There is a significant decrease in the rate of catabolism of horseradish peroxidase pinocytized by proximal renal tubular epithelium in C-HS animals when compared to normal controls. Normal animals catabolize essentially all of the protein by 48 hours post inoculation, whereas C-HS take 96 hours or longer to do the same job. The retained peroxidase is located around the periphery of the granules based on light and electron microscopy. It appears that there is inadequate mixing of substrate and enzyme within the enlarged lysosomes of C-HS animals. In vitro studies on isolated intact lysosomes have demonstrated a 2 to 3 fold higher Km for these enzymes: acid phosphatase, beta-Glucuronidase, and Cathepsin (A B C and D) in C-HS lysosomes when compared to normal. This suggests a better enzyme substrate interaction in the normal lysosome than in C-HS lysosomes. Current studies suggest that the difference in Km is more likely related to volume rather than surface area of the C-HS. C-HS platelets from mice, mink, and cattle do not bind serotonin. We are currently studying the relationship of this lack of serotonin to the bleeding tendency which is present in C-HS individuals.